Introduction

Hepatic ischemia-reperfusion injury (IRI) can occur during surgical resection following prolonged portal triad clamping, during liver transplantation, or in systemic low-flow or hypoxic conditions, such as hemorrhage, sepsis, trauma, or cardiorespiratory failure. The pathophysiology of hepatic IRI is complex and involves multiple molecular and cellular mediators that initiate inflammatory responses, ultimately leading to cell necrosis and apoptosis [1]. During hepatic IRI, Kupffer cells (KCs), liver-resident macrophages, and neutrophils initiate cellular damage by producing inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and reactive oxygen species (ROS), thereby exacerbating hepatic injury [2,3].

Infliximab is a recombinant chimeric human/mouse immunoglobulin G1 monoclonal antibody composed of human heavy chains and mouse variable fragments [4]. This antibody interacts with soluble and transmembrane forms of TNF-α, thereby neutralizing TNF-α by interrupting its interaction with receptors [5]. Previous studies demonstrated that suppression of TNF-α activity with infliximab treatment could protect the liver from IRI [2,6]

The spleen is a lymphoid organ that regulates immune responses and modulates cytokine activity. During hepatic ischemia-reperfusion (IR), the spleen exhibits significant congestion and parenchymal damage, which are associated with an increased production of inflammatory cytokines. In addition, the spleen influences the infiltration of macrophages and neutrophils into the liver and other organs, thereby exacerbating hepatic IRI [7]. Splenectomy alleviates hepatic IRI by decreasing neutrophil infiltration [8], reducing the release of ROS into the hepatic sinusoids [9], and suppressing TNF-α release [7].

To the best of our knowledge, no studies have examined or compared the effects of infliximab and splenectomy on hepatic ischemic injury to date. This study aimed to investigate the inhibitory effect of infliximab on TNF-α in hepatic ischemic injury, focusing on inflammatory responses, oxidative stress, and apoptosis, and to compare these effects with those of splenectomy.

Methods

Ethics statement: All experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Yeungnam University College of Medicine (IACUC No: YUMC-AEC 2017-21).

1. Animals

Male Sprague-Dawley rats weighing 270 to 300 g were used in this study (Central Lab Animal Inc., Seoul, Korea).

2. Experimental groups

Overall, 24 rats were randomly assigned to four groups: (1) sham operation (sham group), (2) hepatic IR (hepatic IR group), (3) hepatic IR with 10 mg/kg infliximab (infliximab group), and (4) hepatic IR with splenectomy (splenectomy group). Each group consisted of six rats. Infliximab (Remicade; Janssen Biotech, Inc., Horsham, PA, USA) was administered intraperitoneally 1 hour before surgery [10], and splenectomy was performed immediately before hepatic ischemia [8].

3. Surgical procedures

The rats were anesthetized and maintained under 2% to 3% sevoflurane during surgery. Body temperature was maintained between 36.5°C and 37.5°C using a heating pad. Midline laparotomy was performed after shaving the abdominal region and cleaning it with an antiseptic solution. Liver ischemia was induced by clamping the left lateral branch of the hepatic artery and portal vein with a microvascular clamp, resulting in approximately 70% hepatic ischemia. Reperfusion was initiated after 30 minutes of ischemia. After 2 hours of reperfusion, blood samples were collected from the heart to assess liver enzyme activity. For biochemical assays, liver tissue samples were harvested from the left lobe and stored in liquid nitrogen at –80°C.

4. Measurement of liver enzyme activity

Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were assessed using a colorimetric assay with a BS-380 analyzer following the manufacturer’s protocol (Asan Pharmacy, Seoul, Korea).

5. Oxidative stress analysis of hepatic tissues

Liver malondialdehyde (MDA) levels were analyzed spectrophotometrically using thiobarbituric acid reactive substances (TBARS; Alfa Aesar, Ward Hill, MA, USA) [11]. The reaction mixture, consisting of tissue homogenate, 0.375% TBARS, 15% trichloroacetic acid (Sigma-Aldrich, St. Louis, MO, USA), and 0.25 N HCl, was heated in a water bath at 100°C for 15 minutes. The mixture was then cooled and centrifuged at 12,000 revolution/min (rpm) for 10 minutes. Absorbance was measured at 535 nm. Tissue protein concentration was determined using a Bradford assay (Bio-Rad, Hercules, CA, USA), and MDA content was expressed as nmol/mg protein.

Superoxide dismutase (SOD) activity was measured by pyrogallol autoxidation [12]. The reaction mixture (pH 8.2) consisted of 50 mM Tris-HCl and 900 μL of 1 mM pentetic acid buffer with 0.1 mM ethylenediaminetetraacetic acid. Three hundred milligrams of liver tissue cell homogenate was added to 20 nM pyrogallol solution (Sigma-Aldrich) to initiate the reaction. Changes in the absorbance associated with pyrogallol autoxidation were analyzed at 420 nm for 1 minute. Protein concentration was determined using the Bradford assay (Bio-Rad). The SOD activity was expressed as U/mg protein by calculating the amount of enzyme required to inhibit the color change by 50%.

6. Western blot analysis of hepatic tissue

Liver tissue samples were homogenized in radioimmunoprecipitation assay buffer (Thermo Fisher Scientific, Rockford, IL, USA) using a homogenizer (Kontes Glass, Vineland, NJ, USA). The resulting supernatant was collected following centrifugation at 12,500 rpm for 20 minutes at 4°C. The total protein content was subsequently analyzed using the Bradford assay (Bio-Rad). The extracts were mixed with loading buffer solution (60 mM Tris-HCl, 2% sodium dodecyl sulfate, 25% glycerol, 0.1% bromophenol blue, and 14.4 mM 2-mercaptoethanol), electrophoresed on a 10% sodium dodecyl sulfate-polyacrylamide gel, and transferred onto nitrocellulose membranes (Whatman GmbH, Dassel, Germany). The membranes were blocked for 2 hours at 22°C to 24°C with 1% bovine serum albumin in Tris-buffered saline with 0.1% Tween 20 (TBST). After washing, the membranes were incubated overnight at 4°C with gentle agitation in TBST containing primary antibody against TNF-α, nuclear factor kappa B (NF-κB), caspase-3, or Bax (diluted 1:1,000; Santa Cruz Biotechnology, Santa Cruz, CA, USA). The membranes were also incubated with primary antibody against β-actin (diluted 1:5,000; Cell Signaling Technology, Beverly, MA, USA). Subsequently, the membranes were washed, incubated with horseradish peroxidase-conjugated secondary antibodies (diluted 1:1,000; Cell Signaling Technology), developed using enhanced chemiluminescence (Advansta Inc., Menlo Park, CA, USA), and analyzed using an Agfa Medical X-ray System (Agfa-Gevaert Group, Mortsel, Belgium). The signal intensity of each band was measured using the National Institutes of Health ImageJ software (ver. 1.47; National Institutes of Health, Bethesda, MD, USA).

7. Statistical analysis

Statistical analyses were performed using the IBM SPSS for Windows ver. 25.0 (IBM Corp., Armonk, NY, USA). Results are expressed as the mean±standard deviation. After assessing normality using the Shapiro-Wilk test, a one-way analysis of variance was performed, followed by a post hoc Tukey test for multiple comparisons. A p-value of <0.05 was considered statistically significant.

Results

1. Liver enzymes

Serum AST and ALT levels were significantly higher in the hepatic IR group than in the sham group (AST: 95% confidence interval [CI], –1,395 to –1,028; p<0.001; ALT: 95% CI, –1,541.5 to –1,003.8; p<0.001). These levels were significantly lower in the infliximab and splenectomy groups than in the hepatic IR group (infliximab: 95% CI, 465.2–832.2; p<0.001; splenectomy: 95% CI, 706.3–1,073.3; p<0.001). Splenectomy resulted in a greater reduction in AST levels than that obtained with infliximab treatment (95% CI, 57.7–424.7; p<0.001) (Fig. 1).

2. Assessment of oxidative stress

MDA levels were higher in the hepatic IR group than in the sham group (95% CI, –0.022 to –0.009; p<0.001). The infliximab treatment and splenectomy groups had significantly lower MDA levels than the hepatic IR group (infliximab: 95% CI, 0.002–0.016; p=0.006; splenectomy: 95% CI, 0.006–0.019; p<0.001) (Fig. 2A). SOD levels were higher in the hepatic IR group than in the sham group (95% CI, 0.037 to –0.153; p<0.001). However, there were no statistically significant differences in SOD levels between the hepatic IR group and the two treatment groups (Fig. 2B).

3. Inflammatory cytokine levels

Hepatic IR resulted in a significant increase in TNF-α and NF-κB levels compared to those in the sham group (TNF-α: 95% CI, –42,087.6 to –35,664.2; p<0.001; NF-κB: 95% CI, –33,148.1 to –29,496.3; p<0.001). In comparison with the hepatic IR group, TNF-α levels were lower in the infliximab and splenectomy groups (infliximab: 95% CI, 17,202.9–23,626.3; p<0.001; splenectomy: 95% CI, 27,800.4–34,223.8; p<0.001), with a more pronounced reduction observed in the splenectomy group (95% CI, 7,385.8–13,809.2; p<0.001) (Fig. 3A). Similar results were observed for NF-κB levels, which were lower in the infliximab and splenectomy groups than in the hepatic IR group (infliximab: 95% CI, 12,233.0–15,884.8; p<0.001; splenectomy: 95% CI, 24,136.1–27,788.0; p<0.001), with a more pronounced reduction in the splenectomy group than in the infliximab group (95% CI, 10,077.2–13,729.1; p<0.001) (Fig. 3B).

4. Assessment of apoptosis

There were no statistically significant differences in Bax levels between the hepatic IR group and the two treatment groups (Fig. 4A). In contrast, caspase-3 activity was significantly higher in the hepatic IR group than in the sham group (95% CI, –6.441 to –2.040; p<0.001), and both infliximab and splenectomy attenuated this upregulation compared with that of the hepatic IR group (infliximab: 95% CI, 0.834–5.234; p=0.005; splenectomy: 95% CI, 0.914–5.314; p=0.004) (Fig. 4B).

Discussion

This study demonstrated that infliximab and splenectomy mitigated hepatic IRI in rats by decreasing liver enzyme (AST and ALT), prooxidant (MDA), and apoptosis-related factor (Bax and caspase-3) levels, and increasing antioxidant activity (SOD).

IRI results from the interplay between complex mechanisms. During ischemia, endothelial cells undergo changes in membrane potential, ion distribution, and cellular swelling, leading to the upregulation of inflammatory cytokines and increased susceptibility to reperfusion injury [13]. After reperfusion, inflammatory cytokines disrupt microcirculation through vasoconstriction, leukocyte entrapment, and platelet aggregation and induce intracellular swelling and hypoxia [13]. Subsequently, KCs and neutrophils are activated, stimulating the production of ROS and proinflammatory cytokines such as TNF-α [3,4].

TNF-α is a critical inflammatory mediator in the progression of IR injury, inducing the formation of ROS and apoptotic cell death, which is associated with NF-κB expression [14]. NF-κB, a nuclear transcription factor present in the cytoplasm, regulates numerous proinflammatory cytokines during IRI through gene transcription [15]. Yucel et al. [4] reported that infliximab decreases TNF-α levels and mitigates histopathological changes induced by hepatic IRI. Similarly, Akdogan et al. [6] demonstrated a protective effect of infliximab on hepatic cells by reducing TNF-α and NF-κB gene expression. In the present study, TNF-α and NF-κB levels increased in the hepatic IRI group and decreased following infliximab treatment.

The spleen is the largest immune organ, with activated neutrophils closely connected to its function. Splenic monocytes/macrophages serve as key mediators in hepatic IRI [9]. Prior splenectomy ameliorates hepatic IRI by reducing neutrophil infiltration into the liver [8] and limiting the release of ROS into the hepatic sinusoids [9]. Belinga et al. [16] reported that splenectomy downregulates NF-κB in the brain following middle cerebral artery occlusion in rats, whereas Nagata et al. [10] demonstrated the protective effects of splenectomy against renal IRI in rats. In the present study, TNF-α and NF-κB levels decreased following splenectomy compared to those in the hepatic IRI group. Consistent with previous findings [10], we observed that TNF-α and NF-κB are important cytokines that induce hepatic IRI and further support the concept that the spleen has a distinct humoral relationship with the liver.

Oxidative stress, along with elevated proinflammatory cytokine levels, is a key pathophysiological mechanism. Oxidative damage arises from an imbalance between prooxidant and antioxidant levels. Excessive ROS levels activate signaling pathways that induce detrimental cellular responses, causing inflammation and necrosis/apoptosis [17,18]. During IRI, mitochondrial dysfunction enhances ROS formation, which consequently induces lipid peroxidation in cell membranes [19]. Among the various biomarkers of lipid peroxidation, the reactive aldehyde MDA is widely recognized as a reliable indicator of oxidative stress in IRI [20]. In contrast to ROS, endogenous antioxidants effectively attenuate oxidative stress in hepatic IRI and can be used to assess oxidative stress levels. SOD, an enzymatic defense system, functions as a major ROS scavenger. Tasdemir et al. [21] reported that infliximab decreases MDA levels and increases SOD levels in renal IR rats. Similarly, Savas et al. [22] demonstrated that splenectomy before intestinal IR attenuated the elevation in serum MDA levels. In the present study, MDA levels were significantly lower in the infliximab and splenectomy groups than in the hepatic IR group, indicating a potential link between TNF-α inhibition and the attenuation of inflammatory responses and oxidative stress. However, the lack of a statistically significant difference in SOD levels between the infliximab and splenectomy groups compared to the hepatic IR group may be attributed to the fact that, although SOD is an important component of the cellular defense system against oxidative stress, its expression and activation are influenced by various signaling pathways beyond TNF-α inhibition [23]. Therefore, the effects of infliximab and splenectomy on SOD activity may be limited. In addition, it is plausible that the reduction in inflammation and oxidative stress (as indicated by decreased MDA levels) achieved with infliximab and splenectomy was sufficient to mitigate oxidative damage without the need for SOD upregulation.

During reperfusion, ROS and inflammatory cytokines damage lipids, proteins, and DNA, and activate apoptosis [24]. Apoptosis is initiated through a complex mechanism involving the binding of TNF-α to its receptor, thereby triggering the apoptosis process [25]. Apoptosis occurs via intrinsic (mitochondrial) and extrinsic pathways, both of which converge upon the activation of caspase-3, leading to DNA fragmentation and apoptosis. The Bcl-2 family is a key regulator of the mitochondrial apoptotic pathway and comprises Bax (proapoptotic) and Bcl-2 (antiapoptotic) [26]. Generally, Bcl-2 decreases cytochrome c release, whereas Bax promotes cytochrome c release and activates caspase-3, thereby inducing apoptosis [26]. Akdogan et al. [27] reported that infliximab reduces caspase-3 activation and attenuates intestinal IRI in rats subjected to the Pringle maneuver. Similarly, Jiang et al. [7] demonstrated that, while hepatic IR upregulates caspase-3 in the liver, splenectomy downregulates its expression. In the present study, hepatic IR upregulated caspase-3 in the liver, whereas infliximab treatment and splenectomy inhibited this upregulation, indicating that infliximab and splenectomy may inhibit apoptosis via the suppression of caspase-3. However, there was no significant difference in Bax expression between the infliximab and splenectomy groups and the hepatic IR group. These different results between Bax and caspase-3 expression indicate that in addition to Bax, other members of the Bcl-2 family involved in the mitochondrial pathway may play critical roles in hepatic IRI. Alternatively, caspase-3 activation may occur via the extrinsic rather than the mitochondrial (intrinsic) apoptotic pathway.

This study had some limitations. First, a single dose of infliximab was administered. Although this approach aligns with previous studies, the effects of varying doses require further investigation. Second, our experimental design did not permit assessment of the time-dependent effects of reperfusion. Given that the functional contributions of cells and mediators can vary with the reperfusion duration in hepatic IRI, further investigations employing different reperfusion times are warranted to elucidate these dynamics. Finally, the relatively small number of animals used per group (n=6) is a limitation of this study and may have influenced the robustness of our conclusions. Future studies with larger sample sizes are necessary to validate these findings and elucidate the underlying mechanisms.

In conclusion, this study demonstrates the protective effects of infliximab and splenectomy against hepatic IRI. TNF-α inhibition, either through infliximab treatment or splenectomy, appears to play a central role in mitigating hepatic IRI. Although the precise mechanisms remain unclear, these protective effects are likely mediated via anti-inflammatory, antioxidative stress, and antiapoptotic pathways within the pathophysiology of hepatic IRI.

Article information

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

This work was supported by a 2024 Yeungnam University Research Grant.

Author contributions

Conceptualization, Formal analysis, Methodology: all authors; Data curation: EKC, SL, DL, YJ; Funding acquisition, Validation: EKC, SL, DL, DGL, KHK, HJ; Investigation: EKC; Resources: DGL, KHK; Software: YJ; Supervision: EKC, DL, DGL, KHK, HJ; Visualization: SL, HJ; Writing-original draft: EKC, SL; Writing-review & editing: all authors.

Fig. 1.

(A) Serum aspartate aminotransferase (AST) and (B) alanine aminotransferase (ALT) levels in the experimental groups (n=6 per group). ^a)p<0.05 vs. sham group, ^b)p<0.05 vs. hepatic IR group, ^c)p<0.05 vs. infliximab group. IR, ischemia-reperfusion; IFX, infliximab; SPLN, splenectomy.

Fig. 2.

(A) Malondialdehyde (MDA) and (B) superoxide dismutase (SOD) levels in the experimental groups (n=6 per group). ^a)p<0.05 vs. sham group, ^b)p<0.05 vs. hepatic IR group. IR, ischemia-reperfusion; IFX, infliximab; SPLN, splenectomy.

Fig. 3.

Densitometry of (A) tumor necrosis factor-alpha (TNF-α), (B) nuclear factor kappa B (NF-κB), and expression relative to β-actin in the experimental groups (n=6 per group). ^a)p<0.05 vs. sham group, ^b)p<0.05 vs. hepatic IR group, ^c)p<0.05 vs. infliximab group. IR, ischemia-reperfusion; IFX, infliximab; SPLN, splenectomy.

Fig. 4.

Densitometry of (A) Bax and (B) caspase-3 expression relative to β-actin in the experimental groups (n=6 per group). ^a)p<0.05 vs. sham group, ^b)p<0.05 vs. hepatic IR group. IR, ischemia-reperfusion; IFX, infliximab; SPLN, splenectomy.

References

• 1. Montalvo-Jave EE, Escalante-Tattersfield T, Ortega-Salgado JA, Piña E, Geller DA. Factors in the pathophysiology of the liver ischemia-reperfusion injury. J Surg Res 2008;147:153–9.ArticlePubMedPMC
• 2. Kaltenmeier C, Wang R, Popp B, Geller D, Tohme S, Yazdani HO, et al. Role of immuno-inflammatory signals in liver ischemia-reperfusion injury. Cells 2022;11:Article
• 3. Oliveira TH, Marques PE, Proost P, Teixeira MM. Neutrophils: a cornerstone of liver ischemia and reperfusion injury. Lab Invest 2018;98:51–62.ArticlePubMedPDF
• 4. Yucel AF, Pergel A, Aydin I, Alacam H, Karabicak I, Kesicioglu T, et al. Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats. Int J Clin Exp Med 2015;8:21287–94.PubMedPMC
• 5. Bagul A. Ischaemic/reperfusion injury: role of infliximab. World J Transplant 2012;2:35–40.ArticlePubMedPMC
• 6. Akdogan RA, Kalkan Y, Tümkaya L, Rakici H, Akdogan E. The effects of infliximab on laminin, NFκB, and anti-TNF expression through its effect on ischemic liver tissue. Gastroenterol Res Pract 2016;2016:1738430.ArticlePubMedPMCPDF
• 7. Jiang H, Meng F, Li W, Tong L, Qiao H, Sun X, et al. Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats. Surgery 2007;141:32–40.ArticlePubMed
• 8. Kato H, Hamada T, Kuriyama N, Ito T, Magawa S, Azumi Y, et al. Role of spleen in hepatic ischemia reperfusion injury: splenic congestion during ischemia accelerates leukocyte infiltration within the liver after reperfusion. Hepatol Res 2017;47:E132–41.ArticlePubMedPDF
• 9. Mizukami T, Yokoyama H, Okamura Y, Ohgo H, Fukuda M, Kamegaya Y, et al. Splenectomy attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide challenge. J Hepatol 1999;31:235–41.ArticlePubMed
• 10. Nagata Y, Fujimoto M, Nakamura K, Isoyama N, Matsumura M, Fujikawa K, et al. Anti-TNF-α agent infliximab and splenectomy are protective against renal ischemia-reperfusion injury. Transplantation 2016;100:1675–82.ArticlePubMed
• 11. Draper HH, Squires EJ, Mahmoodi H, Wu J, Agarwal S, Hadley M, et al. A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials. Free Radic Biol Med 1993;15:353–63.ArticlePubMed
• 12. Kim SJ, Han D, Moon KD, Rhee JS. Measurement of superoxide dismutase-like activity of natural antioxidants. Biosci Biotechnol Biochem 1995;59:822–6.ArticlePubMed
• 13. Serracino-Inglott F, Habib NA, Mathie RT. Hepatic ischemia-reperfusion injury. Am J Surg 2001;181:160–6.ArticlePubMed
• 14. Xu J, Yang Z, Zeng J. Role of NF-kappa B in liver ischemia reperfusion injury of rats. J Huazhong Univ Sci Technolog Med Sci 2003;23:158–60.ArticlePubMedPDF
• 15. Tak PP, Firestein GS. Nf-kappaB: a key role in inflammatory diseases. J Clin Invest 2001;107:7–11.ArticlePubMedPMC
• 16. Belinga VF, Wu GJ, Yan FL, Limbenga EA. Splenectomy following MCAO inhibits the TLR4-NF-κB signaling pathway and protects the brain from neurodegeneration in rats. J Neuroimmunol 2016;293:105–13.ArticlePubMed
• 17. Casillas-Ramírez A, Mosbah IB, Ramalho F, Roselló-Catafau J, Peralta C. Past and future approaches to ischemia-reperfusion lesion associated with liver transplantation. Life Sci 2006;79:1881–94.ArticlePubMed
• 18. Singh R, Czaja MJ. Regulation of hepatocyte apoptosis by oxidative stress. J Gastroenterol Hepatol 2007;22(Suppl 1):S45–8.ArticlePubMed
• 19. Elias-Miró M, Jiménez-Castro MB, Rodés J, Peralta C. Current knowledge on oxidative stress in hepatic ischemia/reperfusion. Free Radic Res 2013;47:555–68.ArticlePubMed
• 20. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014;2014:360438.ArticlePubMedPMCPDF
• 21. Tasdemir C, Tasdemir S, Vardi N, Ates B, Parlakpinar H, Kati B, et al. Protective effect of infliximab on ischemia/reperfusion-induced damage in rat kidney. Ren Fail 2012;34:1144–9.ArticlePubMed
• 22. Savas C, Ozogul C, Karaöz E, Delibas N, Ozgüner F. Splenectomy reduces remote organ damage after intestinal ischaemia-reperfusion injury. Acta Chir Belg 2003;103:315–20.ArticlePubMed
• 23. Che M, Wang R, Li X, Wang HY, Zheng XFS. Expanding roles of superoxide dismutases in cell regulation and cancer. Drug Discov Today 2016;21:143–9.ArticlePubMed
• 24. Lopez-Neblina F, Toledo AH, Toledo-Pereyra LH. Molecular biology of apoptosis in ischemia and reperfusion. J Invest Surg 2005;18:335–50.ArticlePubMed
• 25. Rüdiger HA, Clavien PA. Tumor necrosis factor alpha, but not Fas, mediates hepatocellular apoptosis in the murine ischemic liver. Gastroenterology 2002;122:202–10.ArticlePubMed
• 26. Er E, Oliver L, Cartron PF, Juin P, Manon S, Vallette FM, et al. Mitochondria as the target of the pro-apoptotic protein Bax. Biochim Biophys Acta 2006;1757:1301–11.ArticlePubMed
• 27. Akdogan RA, Kalkan Y, Tumkaya L, Alacam H, Erdivanli B, Aydin İ, et al. Influence of infliximab pretreatment on ischemia/reperfusion injury in rat intestine. Folia Histochem Cytobiol 2014;52:36–41.ArticlePubMed

Figure & Data

References

Citations

Citations to this article as recorded by